Multilayer tablet (also called a multilayered tablet and the like) is a tablet having a multilayer structure consisting of two or more layers, which is used as, for example, one of the dosage forms for combination drugs (patent document 1).
Multilayer tablet can be formed by compressing (tableting) powder materials, which is similar to the case of general core tablets and the like. FIG. 6 is a sectional view of a tableting apparatus, which schematically shows the manner of formation of a multilayer tablet by tableting, wherein a bilayer tablet is produced by tableting as an example.
As shown in FIG. 6(A), one set of a cylindrical shaped die Q10 and the upper and lower punches (upper punch P10 and lower punch P20) is set on a rotary table T10. As shown in the subsequent FIG. 6(B)-(G), while the set of the die and the punches proceeds according to the rotation of the table, stepwise feeding of powder materials into the die, preliminary compression by the upper and lower punches after each feeding, and then final main compression are performed. The completed bilayer tablet 300 is taken out. This series of manufacturing processes is explained in more detail as follows.
First, as shown in FIG. 6 (B), a predetermined amount of a powder material 100 for the first layer is fed from a hopper H10 into a space defined by a lower punch P20 and a die Q10 and, as shown in FIG. 6(C), the upper punch P10 descends following a roll R110, and the powder material 100 is preliminarily compressed by a lower punch P20 supported by a roll R120 and the above-mentioned upper punch P10 to form the first layer 110 in an intermediately-compressed state.
In the example of FIG. 6, a pressing surface of both the upper punch P10 and the lower punch P20 is concave-shaped, namely, both surfaces of a tablet are swollen, forming a convex shape. In this example, therefore, an upper surface of the first layer 110 has a convex-shaped curved surface by being pressed by a concave-shaped pressing surface of the upper punch P10.
Then, as shown in FIG. 6(D), a predetermined amount of a powder material 200 for the second layer is fed from a hopper H20 into a space defined by an upper surface of the first layer 110 and the die Q10 and, as shown in FIG. 6(E), the upper punch P10 descends following a roll R210, and the powder material 200 is preliminarily compressed by the lower punch P20 supported by the roll R120 and the above-mentioned upper punch P10 to form the second layer 210 in an intermediately-compressed state. An upper surface of the second layer 210 is also an upper surface of the whole tablet and, like the upper surface of the first layer 110, has a concave-shaped curved surface by being pressed by the pressing surface of the upper punch P10.
Furthermore, as shown in FIG. 6(F), the upper punch P10 descends following a roll R310 to the final position, and a multilayer body consisting of the first layer and the second layer is mainly compressed by the lower punch P20 supported by a roll R320 and the above-mentioned upper punch P10 to complete the object bilayer tablet 300. As shown in FIG. 6(G), the lower punch P20 rises for the bilayer tablet 300 to be taken out from the die.
One of the main objects of performing preliminary compression for each layer as mentioned above is to confirm the amount of the powder material fed for each layer, via the compressive stress during preliminary compression of each layer. For this end, an upper punch or a lower punch is provided with a load-cell for the stress measurement, and a constitution enabling measurement of the compressive stress upon displacement of the upper punch and/or the lower punch to a preliminary compression position specific to each layer is employed. Whether the volume of each layer (=amount of powder materials) shows variation beyond the defined range is observed through variation of the stress value.
As a result of the preliminary compression of each layer as mentioned above, the upper surface of the first layer 110 is formed first as a compression-packed surface of the powder materials as shown in FIG. 7(a) even though by preliminary compression, and the powder materials of the second layer 210 are compression packed later thereon, and therefore, an interface is formed between the layers, and the close adhesion force between the layers is comparatively low. Therefore, when a conventional bilayer tablet 300 is subject to an impact and the like, layer separation sometimes occurs as shown in FIG. 7(b). In the example of this Figure, the first layer 110 and the second layer 210 are separated at the interface (i.e., upper surface 110a of first layer 110, lower surface 210b of second layer 210).
Conventionally, to suppress such layer separation, for example, the close adhesion force between layers is increased by changing the formulation and powder properties.
However, the above-mentioned measures cannot suppress layer separation sufficiently.